Modeling consequences of localized chronic inflammation in tissue on drug diffusion and exposure caused by prolonged therapy with long-acting formulations.
Modeling and Simulation of the Local Tissue Response to the Long-acting Injectable Formulations
Recently, long-acting injectable (LAI) drug formulations have attracted much attention for prolonged drug exposure from weeks to several months.
Adapting a quantitative systems toxicology model of mitochondrial dysfunction in liver to kidney
Kidney, as a major excretory organ, is exposed to high levels of drugs and their metabolites.
Virtual Patient Generation Strategies for Non-Alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are of growing concern within developed countries, with recent estimates suggesting up to 30% of the US population may be affected.
Mechanistic Analysis of Cisplatin-Induced Acute Kidney Injury Using Quantitative Systems Toxicology Modeling
Acute kidney injury is a common side effect of cisplatin chemotherapy.
The solubility-absorption trade-off in using solubilizers: mechanistic PK simulations of progesterone with explicit cyclodextrin
Cyclodextrins improve solubility of poorly soluble lipophilic drugs due to 1:1 complexation in their nonpolar interior cavity.
Physiologically Based Pharmacokinetic Modeling of Rosuvastatin and Prediction of Transporter-Mediated Drug-Drug Interactions Involving Rifampicin
Statins have been extensively used worldwide for the treatment of cardiovascular diseases.
Development of a Physiologically Based Pharmacokinetic Model for Losartan and Its Active Metabolite E3174 – Ethnic Differences in Pharmacokinetics between Caucasian and Asian Populations
Losartan is a selective, competitive angiotensin II receptor type 1 (AT1) antagonist for hypertension treatment.
Population pharmacokinetic (PopPK) and concentration-QTc analysis of quizartinib in patients (pts) with FLT3-ITD–positive relapsed/refractory (R/R) acute myeloid leukemia (AML)
Fms-related tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells;
signaling through FLT3 promotes their proliferation and differentiation. FLT3 is mutated
in approximately 30% of patients with AML.
Development of a Direct CD8+ T Cell Activation QSP Model for Ovalbumin in the Context of Liver Injury Advances Groundwork for Mathematical Representation of Idiosyncratic Drug-Induced Liver Injury (iDILI)
Extensive progress has been made in identifying mechanisms for dose-dependent drug-induced liver injury (DILI) and in developing screening assays to reduce its incidence.
Assessing Effects of BHV-0223 40 mg Zydis® Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym®
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons that leads to progressive muscle weakness and difficulties in speaking, swallowing, and breathing.
Clarity in Reporting Parameter Variance Needed to Improve Use of Published Models for Simulation Applications
Since published pharmacokinetic and pharmacodynamic models are often used by others for the purpose of simulations, enhanced clarity in reporting and clear statements regarding assumptions will improve the reproducibility of...
A physiologically based pharmacokinetic (PBPK) modeling of amlodipine: High enterocyte binding, not enterohepatic circulation, is responsible for the long Tmax
Amlodipine is a second generation calcium channel blocker that has been widely used in the therapy of hypertension and angina pectoris.
A Simulation and Estimation Platform for Malaria Model Evaluation
Accelerating clinical development of new compounds demands efficient systems for evaluation and interpretation of trial results. Systematizing trial evaluation methods yields efficiency and confidence in results.
Development of a Quantitative Systems Toxicology Model of Drug-Induced Cholangiocyte Injury in DILIsym
Cholangiocyte injury accounts for a quarter of drug-induced liver injury (DILI) cases and is associated with higher rates of morbidity and mortality than hepatocellular DILI (Chalasani et al., 2015).
Zonal Hepatic Stellate Cell (HSC) Activation in Nonalcoholic Steatohepatitis (NASH) Characterized by A Mathematical Model
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of pathophysiology, ranging from hepatic steatosis, through non-alcoholic steatohepatitis (NASH) and hepatic fibrosis, and in rare cases resulting in cirrhosis and liver failure.
Quantitative Systems Toxicology (QST) Supports Differentiated Liver Safety for a Next-in-Class Compound
Lixivaptan, a vasopressin-2 receptor antagonist, is under development for the treatment of autosomal dominant polycystic kidney disease (ADPKD), an orphan disease with minimal treatment options.
Using Quantitative Systems Pharmacology Modeling to Understand the Effects of Acetyl CoA Carboxylase (ACC) Inhibition on Liver and Plasma Triglycerides in a Simulated Population
Treatment options for nonalcoholic steatohepatitis (NASH) are limited. One approach targets hepatic acetyl-CoA carboxylase (ACC), which influences de novo lipogenesis (DNL) and fatty acid oxidation.
In Vitro to In Vivo Extrapolation (IVIVE) of Itraconazole Precipitation using a Biphasic Dissolution Test and Mechanistic Absorption Model
Regulatory agencies have encouraged the use of mechanistic absorption (MAM) and physiologically-based pharmacokinetic (PBPK) modeling to reduce cost and time to market for new and generic drug products.
A Physiologically Based Pharmacokinetic Model of Rivaroxaban: Role of OAT3 and P-gp Transporters in Renal Clearance
Rivaroxaban is an oral anticoagulant which acts by inhibiting factor Xa of the coagulation network.